chr3-119780660-T-C

Variant names:

• chr3-119780660-T-C
• rs1523130
• ENST00000466380:c.-1663T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000466380(NR1I2):​c.-1663T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 152,208 control chromosomes in the GnomAD database, including 20,652 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (20647 hom., cov: 33)
  • Exomes 𝑓: 0.42 (5 hom.)
• Consequence: NR1I2 ENST00000466380 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475

Genes affected

NR1I2 (HGNC:7968): (nuclear receptor subfamily 1 group I member 2) This gene product belongs to the nuclear receptor superfamily, members of which are transcription factors characterized by a ligand-binding domain and a DNA-binding domain. The encoded protein is a transcriptional regulator of the cytochrome P450 gene CYP3A4, binding to the response element of the CYP3A4 promoter as a heterodimer with the 9-cis retinoic acid receptor RXR. It is activated by a range of compounds that induce CYP3A4, including dexamethasone and rifampicin. Several alternatively spliced transcripts encoding different isoforms, some of which use non-AUG (CUG) translation initiation codon, have been described for this gene. Additional transcript variants exist, however, they have not been fully characterized. [provided by RefSeq, Jul 2008]

ENSG00000285585 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000466380	c.-1663T>C		5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000420297.2
ENSG00000285585	ENST00000648112.1	c.*2-26569T>C		intron_variant	Intron 17 of 17			ENSP00000497876.1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72807 AN: 152040 Hom.: 20640 Cov.: 33

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.493

GnomAD4 exome AF: 0.417 AC: 20 AN: 48 Hom.: 5 Cov.: 0 AF XY: 0.471 AC XY: 16 AN XY: 34

Gnomad4 AMR exome AF: 0.750

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.368

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.479 AC: 72831 AN: 152160 Hom.: 20647 Cov.: 33 AF XY: 0.486 AC XY: 36113 AN XY: 74374

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.497

Alfa AF: 0.582 Hom.: 53068

Bravo AF: 0.460

Asia WGS AF: 0.657 AC: 2283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1523130; hg19: chr3-119499507;